The objectives of the proposed research are (1) to find why a non-toxic synthetic pyridine derivative, designated as Compound l, is highly effective in lowering blood cholesterol in rats but is ineffective in monkeys and humans, and (2) through metabolic studies and syntheses relating to Compound 1 to find a drug which will be effective in man. To achieve these objectives, labeled Compound 1 will be administered to rats and monkeys in balance studies and in characterization of metabolites. Metabolites will be synthesized for confirmation of structure and for screening. Based upon these studies, new analogs of Compound 1 will be synthesized for screening as potential agents for atherosclerosis. BIBLIOGRAPHIC REFERENCE: J.E. Sinsheimer, E.V. den Eeckhout, L.E. Hewitt, D.R. Wade, D.W. Hansen, J.C. Drach, and J.H. Burckhalter, Metabolic Formation and Synthesis of 1-(3-Chlorophenyl)-2-(4-hydroxy-phenyl)-1-methyl-2-(2-pyridine)ethanol. A Potential Hypocholesteremic Agent, J. Med. Chem., 19, 647 (1976).